A group of viruses known as retroviruses are of particular concern because they cause diseases that are potentially lethal to an infected host. Retroviruses are a subgroup of RNA viruses that replicate by a reverse transcription mechanism using DNA polymerase that converts viral RNA into proviral DNA which becomes a part of the host cell DNA.
At the present time, several retroviruses are recognized as causative agents of infections in humans. For example, human T cell lymphotropic viruses of type 1 and 2 (HTLV-1 and HTLV-2) are known as the causative agents of T cell leukemia and debilitating neurological diseases. Human immunodeficiency virus (HIV-1 and HIV-2) has been recognized as the causative agent of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC).
HIV can be found in genital secretions, e.g., semen or vaginal fluid, and can be transmitted during sexual intercourse. Thus, AIDS is regarded as a venereal disease with a fatal outcome, and in as many as 80% of the world's cases is caused by the passage of HIV across the genital mucosa. The prevention of the sexual transmission of HIV is an issue of fundamental and paramount importance that needs to be addressed and resolved. Recent clinical surveys have agreed that currently used spermicides with known antiviral activity, e.g., nonoxynol-9, will not satisfactorily restrict the spread of HIV. (Cates et al. Family Planning Perspective, 24:75-84, 1992). Therefore, improved contraceptive agents with virucidal activity are urgently in need of identification, since the majority of the world's AIDS cases are contracted through heterosexual contact. (Merson, Science, 260: 1266-8, 1993).
Gramicidin, which is a cation channel forming ionophore with antibacterial properties, was isolated from a strain of soil bacteria Bacillus brevis by Rene Dubos, a French scientist at the Rockefeller University. Following his initial recovery of a linear pentadecapeptide form in 1941, Soviet scientists reported a cyclic form of gramicidin designated as S. These peptides are remarkably stable natural substances and can retain their biological activity after exposure to extreme variations of temperature. For example, gramicidin S retains its biological activity even after 30 minutes in an autoclave.
Gramicidin is an over-the-counter spermicide routinely used in the former Soviet Union (FSU) as an active component of contraceptive gels and suppositories (Kashkin et al., Antibiotiky, 347-355, 1970). When it is available, millions of units of it are sold in the FSU every year. In Western countries, gramicidin has never been considered or used for spermicidal use. In the United States, gramicidin is used exclusively in topical ophthalmic preparations (Neosporin) in combination with other antibiotics, such as neomycin and polymyxin B with a concentration of less than 0.025% or 25 .mu.g/ml rarely causing irritation as it is poorly absorbed by the skin or mucous membranes. This is probably due to the fact that gramicidin is freely soluble in ethanol, but insoluble in water, acids, and alkalies. In addition to antibacterial activity, gramicidin also exhibits activity against fungal (e.g., Candida albicans), bacterial (gonorrhea) and protozoan (chlamydia) growth. These properties will greatly enhance the potential of gramicidin against conventional sexually transmitted diseases (STDs).
The present inventor has discovered and reported that gramicidin displays useful anti-HIV activity in vitro (Boubinbaiar et al., Life/Sci/Pharmacol. Lett. 54:5-9, 1994) and also can be useful in vivo in the treatment of HIV infection. There are no known reports in the scientific literature demonstrating specifically the direct anti-viral effects of gramicidin, whether in its linear or cyclic forms.
Accordingly, it is a primary object of the present invention to provide a method to prevent the transmission of HIV in vitro.
It is also an object of the present invention to provide a method to prevent the transmission of HIV in vivo during sexual intercourse.
These and other objects of the invention will become apparent from the specification which follows hereafter.